2-Carbomethoxytropinone Explained

2-Carbomethoxytropinone (2-CMT) is a commonly used organic intermediate in the synthesis of cocaine and its analogues.^[1] As of at least 1999 no reaction pathway has been discovered that synthesizes cocaine-like compounds without utilizing the reduction of 2-CMT.^[2] The structure of cocaine was discovered by Richard Willstätter in 1898 after he synthesized it from 2-carbomethoxytropinone.^{[3] [4]} Although it was originally believed that 2-CMT in nature was ultimately derived from ornithine and acetic acid,^[5] subsequent research has indicated other pathways exist for the biosynthesis of 2-CMT.^{[6] [7]} A β-keto ester, 2-CMT exists in equilibrium with its keto–enol tautomer.

Synthesis

2-CMT (3) can be synthesized from 1,3-acetonedicarboxylate anhydride (1) by methanolysis followed by reaction with methylamine and succinaldehyde.^[8]

See also

• Tropinone

Notes and References

1. 10.1021/jo01362a022. Concerning 2-Carbomethoxytropinone*. 1957. Findlay. Stephen P.. The Journal of Organic Chemistry. 22. 11. 1385–1394.
2. 10.1016/S0014-827X(99)00027-0. Two-carbon bridge substituted cocaines: Enantioselective synthesis, attribution of the absolute configuration and biological activity of novel 6- and 7-methoxylated cocaines. 1999. Simoni. Daniele. Roberti. Marinella. Andrisano. Vincenza. Manferdini. Monica. Rondanin. Riccardo. Invidiata. Francesco Paolo. Il Farmaco. 54. 5. 275–87. 10418122.
3. 10.1039/b001713m. Tropane alkaloid biosynthesis. A century old problem unresolved. 2001. Humphrey. Andrew J.. O'Hagan. David. Natural Product Reports. 18. 5. 494–502. 11699882.
4. 10.1021/ja01640a001. The Three-dimensional Structure of the Cocaines. Part I. Cocaine and Pseudococaine. 1954. Findlay. Stephen P.. Journal of the American Chemical Society. 76. 11. 2855–2862.
5. 10.1021/ja00360a038. Chemistry of the tropane alkaloids. 33. 2-Carbomethoxy-3-tropinone: An advanced intermediate in the biosynthesis of cocaine. 1983. Leete. Edward. Journal of the American Chemical Society. 105. 22. 6727–6728.
6. 10.1021/ja00217a051. A revision of the generally accepted hypothesis for the biosynthesis of the tropane moiety of cocaine. 1988. Leete. Edward.. Kim. Sung Hoon.. Journal of the American Chemical Society. 110. 9. 2976.
7. Book: 10.1016/B978-0-12-408061-4.00002-X. Increasing the Pace of New Discoveries in Tropane Alkaloid Biosynthesis. New Light on Alkaloid Biosynthesis and Future Prospects. Advances in Botanical Research. 2013. Jirschitzka. Jan. Dolke. Franziska. d’Auria. John C.. 9780124080614. 68. 39.
8. Proc F. according to Findlay